Abstract
Sulfonamide drugs are well known antibacterial and antimicrobial molecules for pharmaceutical development. Building a library of suitable supramolecular synthons for the sulfonamide functional group and understanding their crystal structures with partner coformer molecules continues to be a challenge in crystal engineering. Although a few sulfonamide cocrystals with amides and N-oxides have been reported, the body of work on sulfonamide synthons is limited compared with those that have carb-oxy-lic acids and carboxamides. To address this structural gap, the present work is primarily focused on sulfonamide-lactam and sulfonamide-syn-amide synthons with drugs such as celecoxib, hydro-chloro-thia-zide and furosemide. Furthermore, the electrostatic potential of previously reported cocrystals has been recalculated to show that the negative electrostatic potential on the lactam and syn-amide O atom is higher compared with the charge on carboxamide and pyridine N-oxide O atoms. The potential of sulfonamide molecules to form cocrystals with syn-amides and lactams are evaluated in terms of the electrostatic potential energy for the designed supramolecular synthons.
Highlights
Obtaining structural data on supramolecular synthons of the sulfonamide group remains a challenge due to the complexity of this functional group with multiple hydrogen-bond donors and acceptors
Our results show that syn-amides are stronger hydrogen-bond acceptors than N-oxides based on MEPEcalculated electrostatic charges for predicting competitive hydrogen-bonding preferences in a competitive environment
To better understand the concept of the sulfonamide donor with multiple acceptor coformers, the energy and enthalpic advantage in heterosynthons and cocrystal formation MEPSES were calculated in different media, such as gas, water, nonpolar (THF) and polar (DMF) solvents
Summary
Obtaining structural data on supramolecular synthons of the sulfonamide group remains a challenge due to the complexity of this functional group with multiple hydrogen-bond donors and acceptors. The molecular electrostatic potential energy (MEPE) surfaces and structural data show a competitive hydrogen-bonding hierarchy between the sulfonamide– syn-amide and sulfonamide–N-oxide supramolecular synthons. CEL (100 mg, 0.26 mmol) and MeTFHP (46 mg, 0.26 mmol) in a 1:1 ratio were ground for 20 min by liquidassisted grinding using EtOAc. The ground mixture was dissolved in EtOAc until the solute dissolved at 40–50C and the solution was filtered by gravity for crystallization at room temperature. CEL (100 mg, 0.26 mmol) and OMeHP (33 mg, 0.26 mmol) were ground for 20 min through liquid-assisted grinding using EtOAc. The ground mixture was dissolved in EtOAc until the solute dissolved at 40–50C and the clear solution was filtered by gravity to afford diffraction-quality single crystals after one week (m.p. 385 K)
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